Leucinamide → HCID 66997131, compound

HRID 2363643Notes

Reaction equation

HRID 2363643 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[N:8]=[C:7]([N:9]2[CH2:13][C@@H:12]3[C@H:14](C4C=C(Br)C=CC=4S([O-])(=O)=O)[CH2:15][CH2:16][C@@H:11]3[CH2:10]2)[CH:6]=[CH:5][CH:4]=1.[NH2:30][C@@H:31]([CH2:35][CH:36]([CH3:38])[CH3:37])[C:32]([NH2:34])=[O:33]>C(#N)C>[F:28][C:2]([F:29])([F:1])[C:3]1[N:8]=[C:7]([N:9]2[CH2:13][C@@H:12]3[C@@H:14]([NH:30][C@H:31]([C:32]([NH2:34])=[O:33])[CH2:35][CH:36]([CH3:38])[CH3:37])[CH2:15][CH2:16][C@@H:11]3[CH2:10]2)[CH:6]=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 69640LeucinamideHCID 86659291HCID 86659291, compound

Product 1

HCID 66997131HCID 66997131, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

The title compound was prepared by combining (3aR,4R,6aS)-2-(6-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-yl-4-bromobenzenesulfonate from Step 4 (150 mg, 0.305 mmol) and (S)-2-amino-4-methylpentanamide (119 mg, 0.916 mmol) in acetonitrile (0.2 mL). The reaction mixture was heated at 85° C. for 3 days, and the acetonitrile was evaporated. This material was purified using a 12 g silica gel cartridge eluted with a gradient of 0-3% methanol (2 N ammonia)/dichloromethane over 20 minutes to give crude product. It was further purified on 2×0.25 mm thin-layer chromatography plate eluted with 45% methanol (2 N ammonia)/dichloromethane to give N2-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.25 (s, 1H), 7.99 (s, 1H), 7.52 (t, J=7.9, 1H), 6.98 (d, J=7.2, 1H), 6.49 (d, J=8.6, 1H), 3.60 (dd, J=10.6, 9.0, 1H), 3.55-3.40 (m, 3H), 3.24 (dd, J=10.8, 3.7, 1H), 3.17 (dd, J=10.2, 5.7, 1H), 2.83-2.71 (m, 1H), 2.64-2.55 (m, 1H), 2.30-2.10 (bs, 1H) 2.08-1.93 (m, 3H), 1.76 (ddd, J=13.5, 8.1, 5.5, 1H), 1.71-1.64 (m, 1H), 1.58 (dd, J=12.7, 5.8, 1H), 1.31 (dd, J=12.7, 5.9, 1H), 0.96 (d, J=6.6, 3H), 0.93 (d, J=6.6, 3H); MS (ESI+) m/z 385 (M+H)+.

Workup

  1. customThe title compound was prepared
  2. customthe acetonitrile was evaporated
  3. customThis material was purified
  4. washeluted with a gradient of 0-3% methanol (2 N ammonia)/dichloromethane over 20 minutes
  5. customto give crude product
  6. customIt was further purified on 2×0.25 mm thin-layer chromatography plate
  7. washeluted with 45% methanol (2 N ammonia)/dichloromethane

Sources & evidence

ORD record
ord-3d9fc4dbb05a489b9db422b6f5199c1e
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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